Altered dynamics of neurovascular coupling in CADASIL

Abstract

Background and ObjectiveNeurovascular coupling is the complex biological process that underlies use‐dependent increases in blood flow in response to neural activation. Neurovascular coupling was investigated at the early stage of CADASIL, a genetic paradigm of ischemic small vessel disease.MethodsFunctional hyperemia and evoked potentials during 20‐ and 40‐sec visual and motor stimulations were monitored simultaneously using arterial spin labeling‐functional magnetic resonance imaging (ASL‐fMRI) and electroencephalography.ResultsCortical functional hyperemia differed significantly between 19 patients and 19 healthy individuals, whereas evoked potentials were unaltered. Functional hyperemia dynamics, assessed using the difference in the slope of the response curve between 15 and 30 sec, showed a time‐shifted decrease in the response to 40‐sec neural stimulations in CADASIL patients. These results were replicated in a second cohort of 10 patients and 10 controls and confirmed in the whole population.InterpretationAlterations of neurovascular coupling occur early in CADASIL and can be assessed by ASL‐fMRI using a simple marker of vascular dysfunction.

Vascular Cognitive Impairment and Dementia

“…Experimental studies have amply demonstrated that hypertension and aging, 2 leading risk factors for VaD and SVD, have profound impact on vessel wall structure and CBF regulation (57,58). Recent human studies using BOLD or arterial spin labeling-MRI provided convincing evidence that cerebrovascular reactivity is altered in patients with SVD (59,60). Moreover, a recent post-mortem study in patients with VaD showed that endothelium-dependent arteriolar dilation was significantly reduced in the WM-penetrating arterioles (61).…”

The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes

“…Importantly, disturbances in blood flow and the processes that regulate it are increasingly appreciated to play a key role in a variety of pathological conditions. These include dementias such as Alzheimer's disease (AD) (Alsop et al, 2000;Iadecola, 2004;Nicolakakis and Hamel, 2011;Iturria-Medina et al, 2016), small vessel disease of the brain (Dabertrand et al, 2015;Capone et al, 2016;Huneau et al, 2018), psychological conditions such as schizophrenia (Mathew et al, 1988;Zhu et al, 2017) and chronic stress (Longden et al, 2014;Han et al, 2019), plus diabetes (Mogi and Horiuchi, 2011;Vetri et al, 2012), hypertension (Girouard and Iadecola, 2006;Capone et al, 2012), and stroke (Girouard and Iadecola, 2006;Koide et al, 2012;Balbi et al, 2017), and pericytes appear to be exceptionally sensitive to pathological perturbations (Winkler et al, 2011).…”

Prospects for Diminishing the Impact of Nonamyloid Small-Vessel Diseases of the Brain

“…Cerebral hypoperfusion, particularly in the white matter, has been documented in sporadic SVDs and CADASIL, although it is not yet clear whether a reduction in CBF is a causative factor or a secondary response to the reduced metabolic demand of the injured brain (41). Furthermore, functional MRI studies have provided convincing evidence that cerebrovascular reactivity-the CBF increase in response to neuronal activation or a vasodilatory stimulus, such as inhaled carbon dioxide (CO2)-is an early alteration in patients with sporadic SVD or CADASIL (40,42).…”